Source:http://linkedlifedata.com/resource/pubmed/id/21569845
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3-5
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| pubmed:dateCreated |
2011-7-1
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| pubmed:abstractText |
The ability of inhibitors of transcription and translation to prevent glucocorticoid-induced apoptosis has been interpreted to indicate that the cell death machinery requires de novo protein synthesis. The transcriptional inhibitors actinomycin D (Act D) and DRB as well as the translational inhibitors CHX and puromycin inhibited early loss of mitochondrial membrane integrity in a dose-dependent manner. This effect was not observed with the transcriptional inhibitor ?-amanitin suggesting they may have additional effects. Their role in the glucocorticoid receptor (GR) intracellular trafficking was therefore investigated. Here, we show that Act D and CHX reduced glucocorticoid binding, GR turnover and impaired GR nuclear translocation. We performed the same experiments in different thymocyte subpopulations of Balb/c mice. At the highest dose tested, actinomycin D and cycloheximide abolished glucocorticoid-induced cell death of CD4+CD8+ and CD4+CD8-. In all subsets, Act D, DRB, as well as CHX and puromycin prevented receptor nuclear translocation, indicating a general alteration of GR trafficking. Overall, our data support a direct effect of macromolecular inhibitors on GR activation and trafficking. Finally, direct alterations of the functional properties of the glucocorticoid receptor might be responsible for cell death prevention by actinomycin D, DRB, cycloheximide and puromycin.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alpha-Amanitin,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Glucocorticoids,
http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleic Acid Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Synthesis Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Puromycin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Glucocorticoid
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1879-1220
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| pubmed:author | |
| pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
126
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
104-12
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| pubmed:meshHeading |
pubmed-meshheading:21569845-Alpha-Amanitin,
pubmed-meshheading:21569845-Animals,
pubmed-meshheading:21569845-Cells, Cultured,
pubmed-meshheading:21569845-Cycloheximide,
pubmed-meshheading:21569845-Dactinomycin,
pubmed-meshheading:21569845-Glucocorticoids,
pubmed-meshheading:21569845-HeLa Cells,
pubmed-meshheading:21569845-Humans,
pubmed-meshheading:21569845-Macromolecular Substances,
pubmed-meshheading:21569845-Mice,
pubmed-meshheading:21569845-Mice, Inbred BALB C,
pubmed-meshheading:21569845-Nucleic Acid Synthesis Inhibitors,
pubmed-meshheading:21569845-Protein Binding,
pubmed-meshheading:21569845-Protein Synthesis Inhibitors,
pubmed-meshheading:21569845-Protein Transport,
pubmed-meshheading:21569845-Puromycin,
pubmed-meshheading:21569845-Receptors, Glucocorticoid,
pubmed-meshheading:21569845-Thymus Gland
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| pubmed:year |
2011
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| pubmed:articleTitle |
Macromolecular synthesis inhibitors perturb glucocorticoid receptor trafficking.
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| pubmed:affiliation |
Jean-Pierre Aubert Research Center, Lille, France.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Evaluation Studies
|